Intellectual Merit: Biological cells can cope with processing bottlenecks and also leverage the dynamics of bottlenecks to robustly control cellular behavior. This realization prompts a re-evaluation of the fundamental design principles believed to govern biological circuits. This project will investigate synthetic and native circuits in E. coli that are known to experience bottlenecks stemming from the competition of basic cellular components (created, modified, or degraded) for the shared molecular machinery. The experimental data combined with the theoretical predictions will allow the development and validation of queueing theoretical principles relevant to biological systems. Queueing theory is commonly applied to resolve performance limitations in traffic and communications systems. Fluorescence microscopy, microfluidics, and synthetic biology will be combined with quantitative modeling to probe protein degradative mechanisms and stress response pathways in terms of queueing theory in E. coli. Successful accomplishment of this project will lead to effective strategies for the synthesis and understanding of biological circuits that either avoid or exploit processing bottlenecks to perform specific tasks. The successful demonstration of the biological queueing theory is likely to impact also the more traditional disciplines, including telecommunication networks, call centers and transportation systems.
Broader Impacts: Part of this project will lead to the construction of new content for elementary school STEM education with a specific emphasis on the interdisciplinary aspect of science. This will be done largely through close collaboration with Kids' Tech University (KTU), a successful elementary school program at Virginia Tech with the single goal to create "the future workforce in science, technology, engineering, and mathematics (STEM) by sparking kids' interest in these fields." This collaboration will result in the generation, presentation, and distribution of interactive booths to illustrate interdisciplinary phenomena related to this project. Graduate and undergraduate students will be mentored in service learning to ensure effective outreach and to provide these students with teaching experience. Undergraduates will be supported to construct modules for Virtual KTU, which freely provides interactive web-based demonstrations of STEM topics to students of all ages and educators.
